Effects of the enantiomers of lansoprazole (AG-1749) on (H+ + K+)-ATPase activity in canine gastric microsomes and acid formation in isolated canine parietal cells

Abstract The effects of the enantiomers of 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy) - 2 - pyridyl]methyl]sulfinyl] - 1 H - benzimidazole(lansoprazole, AG-1749) on acid formation in isolated canine parietal cells and (H + + K + )-ATPase activity in canine gastric microsomes were investigated. Both the (+)-and the (−)-enantiomer of lansoprazole inhibited the acid formation stimulated by dibutyryl cyclic AMP (db-cAMP) in isolated canine parietal cells in a concentration-dependent manner with IC 50 values of 59 and 82 nM, respectively. The enantiomers showed concentration-dependent inhibition of (H + + K + )-ATPase with IC 50 values of 4.2 and 5.2 μM, respectively. On the other hand, the IC 50 values of lansoprazole for db-cAMP-stimulated acid formation and (H + + K + )-ATPase were 59 nM and 2.1 μM, respectively. These results suggest that the two enantiomers of lansoprazole have antisecretory action due to inhibition of (H + + K + )-ATPase.